1. Field of Invention
This invention relates to a carrier base material to be combined with a therapeutically active medicament and formed into a solid, shaped unit dosage form having a controlled and prolonged incremental release of the medicament upon administration. Specifically, this invention relates to a mixture of a water-soluble nonionic cellulose ether and an anionic surface active agent which is suitable for use in controlled release therapeutic compositions.
2. Description of the Prior Art
Water-soluble nonionic cellulose ethers have been used as binders, matrices or carrier bases in sustained release solid dosage forms containing active medicaments, accompanied by lubricants and excipient fillers, as needed. Methylcellulose and hydroxypropylmethylcellulose, particularly the latter, are among the nonionic cellulose ethers which have been most widely used in this manner.
The cellulose ethers are commercially available in various grades under several trade names. The grades available under a given trade name represent differences in composition and molecular weight. Thus, water-soluble methylcellulose (Methocel A, previously designated as Methocel MC, from The Dow Chemical Co., U.S.A. and Metolose SM from Shin-Etsu, Ltd., Japan) has a methoxyl content of 27.5-31.5 weight-% and is available in various viscosity grades. Hydroxypropylmethylcellulose is actually a series of compounds (Methocel E, F, J and K, all previously designated as versions of Methocel HG, from The Dow Chemical Co., U.S.A., and Metolose SH from Shin-Etsu, Ltd., Japan), each of which has a different chemical composition with a methoxyl content within the range of 16.5 to 30 weight-%, a hydroxypropoxyl content within the range of 4 to 32 weight-% and each of which is available in various viscosity grades.
Commercial designations of the various cellulose ethers are based on the viscosities of 2% aqueous solutions at 20.degree. C. The viscosities range from 5 cps to 100,000 cps and represent number average molecular weights ranging from below 10,000 to over 150,000, as calculated from the data in "Handbook of Methocel Cellulose Ether Products" (The Dow Chemical Co., 1974).
Christenson and Dale (U.S. Pat. No. 3,065,143) and Huber, Dale and Christenson (J. Pharm. Sci., 55, 974 (1966) disclosed the preparation of a sustained release drug tablet wherein a high viscosity grade, i.e. high molecular weight, hydroxypropylmethylcellulose, was present as binder to the extent of at least one third of the weight of the table. The binders included 4000 cps viscosity grade Methocel 60 HG, now known as Methocel E4M, having a 28-30 weight-% methoxyl content, a 7.5-12 weight-% hydroxypropoxyl content and a number average molecular weight of 93,000, as well as 4000 cps and 15,000 cps viscosity grades Methocel 90 HG, now known as Methocel K4M and Methocel K15M, respectively, having a 19-24 weight-% methoxyl content, a 4-12 weight-% hydroxypropoxyl content and number average molecular weights of 89,000 and 124,000, respectively.
Christenson and coworkers proposed that water was rapidly absorbed and formed a gel barrier on the surface of the tablet. Drug release was controlled by drug diffusion from and attrition of the gel barrier.
Christenson and Huber (U.S. Pat. No. 3,590,117) reported that neither low viscosity grade hydroxypropylmethylcellulose nor high viscosity grade, i.e. 15,000 cps, hydroxypropylmethylcellulose made acceptable long-lasting troches.
Lapidus (Dissertation, Rutgers State University, 1967) and Lapidus and Lordi (J. Pharm. Sci., 55, 840 (1966); 57, 1292 (1968) studied the use of high viscosity grade methylcellulose (4000 cps viscosity grade Methocel MC now designated as Methocel A4M) and/or low and high viscosity grade hydroxypropylmethylcellulose (25 cps and 15,000 cps viscosity grade Methocel 90 HG now designated as Methocel K25 and Methocel K15M, respectively) in compressed pharmaceutical tablets and confirmed the proposal of Christenson et al. that drug diffusion and attrition of the hydrated layer determined the rate of drug release.
Salomon, Doelker and Buri (Pharm. Acta Helv., 54 (3), 82 (1979) disclosed the use of 15,000 cps viscosity grade Methocel 90HG (now designated as Methocel K15M) in a tablet containing potassium chloride.
Sheth and Tossounian (U.S. Pat. Nos. 4,126,672; 4,140,755; 4,167,558) disclosed solid dosage forms containign 4000 cps viscosity grade methylcellulose or hydroxypropylmethylcellulose in combination with various additives including gas-generating compounds, e.g. calcium carbonate, and inert fatty materials, so as to be hydrodynamically balanced so that they have a bulk density of less than one in contact with gastric fluid.
Schor, Nigalaye and Gaylord (U.S. Pat. No. 4,389,393) disclosed sustained release solid unit dosage forms in which the carrier base material constituted less than one third of the weight of the dosage form and consisted of hydroxypropylmethylcellulose of at least 4000 cps viscosity grade, having a methoxyl content of 16-24 weight-%, a hydroxypropoxyl content of 4-32 weight-% and a number average molecular weight of at least 50,000, i.e. Methocel J and Methocel K or Metolose 90 SH.
The use of high viscosity grades of methylcellulose Methocel A and hydroxypropylmethylcellulose Methocel E, Methocel F and Methocel K, in sustained release solid drug dosage forms is also described in a technical bulletin "Formulating Sustained Release Pharmaceutical Products with Methocel" (The Dow Chemical Co, 1982).
The cited prior art discloses that high viscosity grades of hydroxypropylmethylcellulose of various chemical compositions are useful in the preparation of sustained release solid drug dosage forms. However, Schor, Nigalaye and Gaylord (U.S. Pat. No. 4,369,172) disclosed that effective prolonged release therapeutic compositions were prepared by using as a carrier base material, a low viscosity grade hydroxypropylmethylcellulose having a hydroxypropoxyl content of 9-12 weight-% and a number average molecular weight of less than 50,000.
Lowey and Stafford (U.S. Pat. No. 3,870,790) and Schor (U.S. Pat. No. 4,226,849) disclosed that effective sustained release tablets were produced by using as carrier base material, a modified low viscosity grade hydroxypropylmethylcellulose having a hydroxypropoxyl content of less than 9 weight-% and a number average molecular weight of 23,000, e.g. Methocel E50. The modification was carried out by exposure of the low molecular weight hydroxypropylmethylcellulose to high humidity or moisture and drying in air, resulting in an increase in the carboxyl content of the polymer.
Lowey (U.S. Pat. No. 4,259,314) disclosed the use of a mixture of hydroxypropylmethylcellulose having a viscosity in the range of 50 to 4000 cps, and hydroxypropylcellulose in the preparation of a controlled release pharmaceutical composition.
The present invention is directed toward further improvements in carrier base materials containing nonionic cellulose ethers for use in the preparation of prolonged release solid pharmaceutical unit dosage forms. These improvements result from the presence of an anionic surfactant.
The addition of 1% of some anionic salts of alkyl sulfates, alkyl sulfonates or alkylaryl sulfonates to 1% aqueous solutions of methylcellulose (Methocel A) or hydroxypropylmethylcelluloses (Methocel E, Methocel F and Methocel K) results in an increase in the viscosity of the cellulose ether solution ("Handbook on Methocel Cellulose Ether Products", The Dow Chemical Co, 1975).
An increase in the rate of solution of a drug results from the presence of anionic surfactants, such as dioctyl sodium sulfosuccinate and/or sodium lauryl sulfate, in the dissolution medium or incorporated into compressed drug tablets, containing water-insoluble binders, including polyethylene (Desai et al., J. Pharm Sci., 54, 1459 (1965); 55, 1224, 1230 (1966), polyvinyl chloride (Desai et al., J. Pharm. Sci., 55, 1235 (1066) and wax (Dakkuri et al, J. Pharm. Sci., 67, 354 (1978); Chambliss, J. Pharm. Sci., 70, 1248 (1981). The presence of sodium lauryl sulfate in a quinine sulfate tablet containing a polyamide binder, decreased the rate of solution of the drug at ph 1.5 but had little effect at pH 7.5 (Choulis et al., Pharmazie, 30, 233 (1975).